A tissue engineered 3D printed calcium alkali phosphate bioceramic bone graft enables vascularization and regeneration of critical-size discontinuity bony defects in vivo.

Introduction: Recently, efforts towards the development of patient-specific 3D printed scaffolds for bone tissue engineering from bioactive ceramics have continuously intensified. For reconstruction of segmental defects after subtotal mandibulectomy a suitable tissue engineered bioceramic bone graft needs to be endowed with homogenously distributed osteoblasts in order to mimic the advantageous features of vascularized autologous fibula grafts, which represent the standard of care, contain osteogenic cells and are transplanted with the respective blood vessel. Consequently, inducing vascularization early on is pivotal for bone tissue engineering. The current study explored an advanced bone tissue engineering approach combining an advanced 3D printing technique for bioactive resorbable ceramic scaffolds with a perfusion cell culture technique for pre-colonization with mesenchymal stem cells, and with an intrinsic angiogenesis technique for regenerating critical size, segmental discontinuity defects in vivo applying a rat model. To this end, the effect of differing Si-CAOP (silica containing calcium alkali orthophosphate) scaffold microarchitecture arising from 3D powder bed printing (RP) or the Schwarzwalder Somers (SSM) replica fabrication technique on vascularization and bone regeneration was analyzed in vivo. In 80 rats 6-mm segmental discontinuity defects were created in the left femur. Methods: Embryonic mesenchymal stem cells were cultured on RP and SSM scaffolds for 7d under perfusion to create Si-CAOP grafts with terminally differentiated osteoblasts and mineralizing bone matrix. These scaffolds were implanted into the segmental defects in combination with an arteriovenous bundle (AVB). Native scaffolds without cells or AVB served as controls. After 3 and 6 months, femurs were processed for angio-µCT or hard tissue histology, histomorphometric and immunohistochemical analysis of angiogenic and osteogenic marker expression. Results: At 3 and 6 months, defects reconstructed with RP scaffolds, cells and AVB displayed a statistically significant higher bone area fraction, blood vessel volume%, blood vessel surface/volume, blood vessel thickness, density and linear density than defects treated with the other scaffold configurations. Discussion: Taken together, this study demonstrated that the AVB technique is well suited for inducing adequate vascularization of the tissue engineered scaffold graft in segmental defects after 3 and 6 months, and that our tissue engineering approach employing 3D powder bed printed scaffolds facilitated segmental defect repair.

Prosthodontic Treatment Outcomes in Periodontally Compromised Patients: A 6- to 20-Year Long-Term Cohort Study.

PURPOSE: To report and analyze long-term treatment outcomes in a patient cohort with severe periodontal disease treated with an employed protocol combining use of implants and double-crown prosthetic support. MATERIALS AND METHODS: A convenience sample of 16 patients with generalized severe periodontal disease were prosthodontically managed with support from 83 dental implants and 21 removable prostheses using a double-crown concept (11 implant-tooth supported and 10 implant supported). Each patient was examined 2 to 4 weeks before scheduled teeth extraction and examined again following treatment completion at the time of insertion of the superstructures. Subsequent recall examinations were performed every 3 months over a 6- to 20-year period. Predetermined clinical parameters were recorded at each session, and intraoral radiographs were taken after insertion of the superstructure and at intervals of 1, 3, 5, 10, and 20 years. RESULTS: No implant or tooth loss occurred during the individual observation periods. Mucositis was recorded around 65% of the implants and was accompanied by additional maxillary marginal bone loss around 27.7% of the implants. Mean marginal bone loss at implant sites after 5 years was 0.75 ± 0.66 mm, and after 20 years was 1.50 ± 1.45 mm. Moderate bone loss around teeth was registered after 5 years (2.8%) and 20 years (7.3%). No significant differences were found between implants in patients with tooth-implant-supported and those with implant-supported double-crown restorations. CONCLUSION: These results suggest that severely periodontally compromised patients can be successfully managed in the long term with the described clinical protocol.

A Double-Crown Concept for Restorations in Patients with Generalized Aggressive Periodontitis: Two Case Reports with 22- and 25-Year Follow-ups.

Implant-supported prosthetics are a suitable option for improving partially and totally edentulous patients' oral life quality, especially those patients with a history of periodontitis who experience early tooth loss and therefore require implant therapy. However, long-term clinical studies on dental implants have indicated that patients with periodontitis show more biologic complications and lower survival and success rates compared to periodontally healthy patients. The two clinical reports presented show that patients with aggressive periodontal diseases treated with a supportive periodontal therapy can be successfully rehabilitated with implant-supported double-crown restorations for a follow-up period of over 20 years.

Effect of silicon-doped calcium phosphate bone grafting materials on bone regeneration and osteogenic marker expression after implantation in the ovine scapula.

Compared to the currently clinically available bone grafting materials for alveolar ridge augmentation, there is a great demand for bioactive bone substitutes with higher resorbability, which enhance osteogenesis at the same time. This has prompted the development of a silicon-doped rapidly resorbable calcium alkali orthophosphate (Si-CAOP) and silicon-doped ß-tricalcium phosphate (Si-TCP). This study evaluated the effect of these two particulate graft materials as compared to the currently clinically used ß-TCP on bone formation and osteogenic marker expression after 2 weeks, 1, 3, 6, 12, and 18 months of implantation in critical size defects in the sheep scapula. Immunohistochemical analysis of collagen type I, alkaline phosphatase, and osteocalcin expression was performed on resin embedded sections. The bone and particle area fraction and the bone-biomaterial contact were determined histomorphometrically. After 2 weeks and 1 month defects grafted with Si-CAOP displayed a significantly greater bone area fraction, bone-particle-contact, osteogenic marker expression and significantly lower particle area fraction than defects grafted with Si-TCP and TCP. By 3 and 6 months all materials studied mediated excellent defect regeneration with further bone remodeling at 12 and 18 months. Taken together, Si-CAOP induced the most expeditious bone regeneration of critical size defects in the sheep scapula. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2018. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 594-614, 2019.

Development of a synthetic tissue engineered three-dimensional printed bioceramic-based bone graft with homogenously distributed osteoblasts and mineralizing bone matrix in vitro.

Over the last decade there have been increasing efforts to develop three-dimensional (3D) scaffolds for bone tissue engineering from bioactive ceramics with 3D printing emerging as a promising technology. The overall objective of the present study was to generate a tissue engineered synthetic bone graft with homogenously distributed osteoblasts and mineralizing bone matrix in vitro, thereby mimicking the advantageous properties of autogenous bone grafts and facilitating usage for reconstructing segmental discontinuity defects in vivo. To this end, 3D scaffolds were developed from a silica-containing calcium alkali orthophosphate, using, first, a replica technique - the Schwartzwalder-Somers method - and, second, 3D printing, (i.e. rapid prototyping). The mechanical and physical scaffold properties and their potential to facilitate homogenous colonization by osteogenic cells and extracellular bone matrix formation throughout the porous scaffold architecture were examined. Osteoblastic cells were dynamically cultured for 7 days on both scaffold types with two different concentrations of 1.5 and 3 × 109 cells/l. The amount of cells and bone matrix formed and osteogenic marker expression were evaluated using hard tissue histology, immunohistochemical and histomorphometric analysis. 3D-printed scaffolds (RPS) exhibited more micropores, greater compressive strength and silica release. RPS seeded with 3 × 109 cells/l displayed greatest cell and extracellular matrix formation, mineralization and osteocalcin expression. In conclusion, RPS displayed superior mechanical and biological properties and facilitated generating a tissue engineered synthetic bone graft in vitro, which mimics the advantageous properties of autogenous bone grafts, by containing homogenously distributed terminally differentiated osteoblasts and mineralizing bone matrix and therefore is suitable for subsequent in vivo implantation for regenerating segmental discontinuity bone defects. Copyright © 2016 John Wiley & Sons, Ltd.

Effect of sex-hormone levels, sex, body mass index and other host factors on human craniofacial bone regeneration with bioactive tricalcium phosphate grafts.

Little is known regarding the associations between sex-hormone levels, sex, body mass index (BMI), age, other host factors and biomaterial stimulated bone regeneration in the human craniofacial skeleton. The aim of this study was to elucidate the associations between these factors and bone formation after sinus floor augmentation procedures (SFA) utilizing a bioactive tricalcium phosphate (TCP) bone grafting material. We conducted a prospective study in a human population in which 60 male and 60 female participants underwent SFA and dental implant placement using a staged approach. BMI as well as levels of serum estradiol (E2), total testosterone (TT), and the free androgen index (FAI) were measured by radioimmunoassay and electrochemoluminescent-immunoassay. At implant placement, 6 months after SFA, bone biopsy specimens were harvested for hard tissue histology, the amount of bone formation was evaluated by histomorphometry and immunohistochemical analysis of osteogenic marker expression. The Wilcoxon rank-sum U test, Spearman correlations and linear regression analysis were used to explore the association between bone formation and BMI, hormonal and other host factors. BMI and log E2 were significantly positively associated with bone formation in male individuals (p < 0.05). Histomorphometry revealed trends toward greater bone formation and osteogenic marker expression with non-smokers compared to smokers. In male patients, higher E2 levels and higher BMI enhanced TCP stimulated craniofacial i.e. intramembranous bone repair.

Dentofacial Composition: An Entire Aesthetic Concept.

The aesthetic appearance of the mouth region, in addition to the eye and nose area, is the impressive element for facial aesthetics. Therefore, the reconstruction of the intraoral region is very important for the facial aesthetics in the case of genetic dysplasia, trauma, or even in cases for rejuvenating purposes only. The entire region is complex so that in many patient cases only the team work of restorative dentists, surgeons, and orthodontists will be effective. A key role is played here by the dental technician. Besides the frequent necessity of osseous augmentation, the mucogingival complex needs to be, in most cases, harmonized and reconstructed, respectively. There is often a lack of keratinized gingiva and disturbing cicatrice tracks. Quite frequently the mucogingival appearance is also unsatisfactory due to preceding operations and attempted plastic coverages. The aim of this report is to describe the successful surgical and prosthetic treatment of aesthetically and functionally impaired intraoral hard and soft tissue. For surgeons who are interested in aesthetics, it is advisable to learn from experiences of a specialized restorative dentist, oral surgeon, and orthodontist.

Soft-tissue grafting for peri-implantitis-a treatment option in case of unsuitable skeletal basic morphology of the alveolar bone and lack of keratinized mucosa: a retrospective clinical cohort study.

BACKGROUND: This retrospective study evaluated soft-tissue grafting as a surgical treatment option for peri-implantitis in case of unsuitable basic skeletal morphology of the alveolar bone and lack of keratinized mucosa. METHODS: Twenty-eight patients (21 females, 7 males, at a mean age 59.4 years) were included with a total of 54 implants. All implants showed peri-implantitis and attached keratinized buccal mucosa of ≤2 mm. A surgical procedure of soft-tissue grafting (STG) was made by inserting an inlay and inlay-onlay transplant. Clinical investigations were made prior to the STG (baseline) and after 9-180 months (Ø 43 months) including the following parameters: soft-tissue biotype, skeletal basic morphology of the alveolar bone, width of the peri-implant keratinized mucosa (KM), mobility of the KM, pocket probing depth (PPD), and bleeding on probing (BOP). RESULTS: Nearly all patients showed a thin soft-tissue biotype. The analysis of the skeletal basic morphology of the alveolar bone revealed a narrow apical base in 18 patients, middle base in 7 patients, and broad base in 3 patients. Width of the KM increased significantly (p < 0.01) from 0.4 ± 0,5 mm to 4.3 ± 1.5 mm after STG and PPD was significantly (p < 0,01) reduced from 6.3 ± 2,3 mm to 4.1 ± 1.9 mm. A significant reduction (p < 0.01) in BOP was recorded. All patients reported a clinical improvement of the inflammatory symptoms at follow-up. CONCLUSIONS: The results of this study showed that the STG can be applied successfully as a surgical treatment of peri-implantitis. It remains unclear whether soft-tissue biotype or the skeletal basic morphology of the alveolar bone affects the outcome of this surgical treatment.

Template-guided flapless implant insertion and prosthetic rehabilitation with telescopic crowns in a patient with treated generalized aggressive periodontitis: a case report.

Implant therapy offers a wide range of possibilities in prosthetics. Especially for completely edentulous patients with early tooth loss due to periodontitis, implant therapy is an option to regain a comfortable, esthetic dental rehabilitation. Several studies have indicated that osseointegrated implants can be placed successfully in periodontally compromised patients but with lower survival and success rates than in uncompromised patients. This case report describes a patient that received periodontal therapy for generalized aggressive periodontitis and achieved prosthetic rehabilitation 16 years later with telescopic crowns by means of template-guided flapless implant insertion. In particular, in patients with a history of periodontitis in which bone loss makes implant planning more complicated and in whom wound healing might be compromised, the approach presented in this paper describes a method that is predictable and minimally traumatic.